Genomic Analysis of Antibiotic Resistant Bacteria

Methicillin-resistant Staphylococcus aureus, also known as MRSA, is an antibiotic-resistant bacteria that infects approximately 90,000 people in the United States each year. This bacteria’s resistance to many common drugs, including penicillin, makes it a rising public health care threat, yet our understanding of MRSA at the genetic level is limited. In order to bridge this gap, scientists at the University of San Diego and Korea Advanced Institution of Science and Technology sequenced the transcriptome—the total mRNA, or genes that are expressed, of a cell in a particularly deadly strain of MRSA known as USA300.

The scientists identified a total of 1,861 transcription start sites in the genome, which are sites in the DNA where the transcription of a gene begins. Additionally, over 200 genes were found to be associated with one or more of these transcription start sites. This means that it is possible to express these genes in more than one way, which suggests that MRSA has a particularly complex gene regulatory system.

In order to identify how MRSA is resistant to antibiotics at the genetic level, the scientists treated the bacteria with three different antibiotics: linezolid, nafcillin, and vancomycin. They then compared the different gene expression patterns of MRSA, and identified a possible tradeoff between pathogenesis and drug resistance. Notably, the scientists also identified genes that were activated upon contact with all three antibiotics. One of these genes, called ComF, aids in the uptake of DNA from the external environment, in a process known as horizontal gene transfer. These results may provide insight into how MRSA is able to adapt to become resistant to multiple antibiotics in a relatively short amount of time.